FUNCTIONAL EQUIVALENCE OF CREATINE-KINASE ISOFORMS IN MOUSE SKELETAL-MUSCLE

Creatine kinase (CK) is a highly conserved enzyme abundant in skeletal muscle that has a key role in high energy phosphate metabolism, The l ocalization of the muscle isoenzyme of CK (MM-CK) to the M line and th e sarcoplasmic reticulum of myofibrils has been suggested to be import ant for proper force development in skeletal muscle, The importance of this subcellular compartmentation has not been directly tested in viv o. To test the role of myofibrilar localization of CR, the consequence s of a complete CR isoform switch from MM-CII to the brain (BE-CIT) is oform, which does not localize to the M Line, was studied in transgeni c mouse skeletal muscle, in RIM-CK knockout mice there are large contr actile defects, When MM-CK was replaced by BE-CK, the aberrant contrac tile phenotypes seen in MIM-CH knockout mice were returned to normal d espite the lack of myofibrillar localization, These results indicate t hat CK compartmentation to the myofibril of skeletal muscle is not ess ential for contractile function and that there is functional equivalen ce of creatine kinase isoforms in supporting cellular energy metabolis m.